Healthy volunteers were randomized into groups receiving different dose combinations of the antiretroviral protease inhibitor agents soft gel cap saquinavir (Saquinavir SGC) and ritonavir versus saquinavir-SGC alone. Combinations were generally well tolerated and safe. Addition of mini-dose ritonavir (100 mg/d) to once daily saquinavir SGC exposure 7 fold and maintained through levels 40-fold higher than the IC90 for HIV. Once daily Didanosire did not alter pharmacokinetics. The study was stopped prematurely because there was not a trend to suggest additional benefit from higher dosages.